EPHB6_MOUSE
ID EPHB6_MOUSE Reviewed; 1014 AA.
AC O08644; Q3TQ77; Q8BN76; Q8K0A9;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 20-APR-2010, sequence version 4.
DT 03-AUG-2022, entry version 194.
DE RecName: Full=Ephrin type-B receptor 6;
DE AltName: Full=MEP;
DE AltName: Full=Tyrosine-protein kinase-defective receptor EPH-6;
DE Flags: Precursor;
GN Name=Ephb6; Synonyms=Cekl;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3), AND TISSUE SPECIFICITY.
RC STRAIN=BALB/C X 129; TISSUE=Thymus;
RX PubMed=8761299;
RA Gurniak C.B., Berg L.J.;
RT "A new member of the Eph family of receptors that lacks protein tyrosine
RT kinase activity.";
RL Oncogene 13:777-786(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Eye, and Head;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=FVB/N; TISSUE=Salivary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
CC -!- FUNCTION: Kinase-defective receptor for members of the ephrin-B family.
CC Binds to ephrin-B1 and ephrin-B2. Modulates cell adhesion and migration
CC by exerting both positive and negative effects upon stimulation with
CC ephrin-B2. Inhibits JNK activation, T-cell receptor-induced IL-2
CC secretion and CD25 expression upon stimulation with ephrin-B2 (By
CC similarity). {ECO:0000250}.
CC -!- SUBUNIT: Interacts with CBL and EPHB1. Interacts with FYN; this
CC interaction takes place in a ligand-independent manner (By similarity).
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane; Single-pass type I
CC membrane protein.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Secreted.
CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Secreted.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Comment=Additional isoforms seem to exist.;
CC Name=1;
CC IsoId=O08644-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O08644-2; Sequence=VSP_003020, VSP_003021;
CC Name=3;
CC IsoId=O08644-3; Sequence=VSP_003022, VSP_003023;
CC -!- TISSUE SPECIFICITY: High level in thymus, and brain. Very low levels of
CC expression in kidney, lung, liver, bone marrow, skeletal muscle, spleen
CC from 2 week old and adult mice, heart, testes and embryonic stem cells.
CC {ECO:0000269|PubMed:8761299}.
CC -!- DOMAIN: The protein kinase domain is predicted to be catalytically
CC inactive. Its extracellular domain is capable of promoting cell
CC adhesion and migration in response to low concentrations of ephrin-B2,
CC but its cytoplasmic domain is essential for cell repulsion and
CC inhibition of migration induced by high concentrations of ephrin-B2 (By
CC similarity). {ECO:0000255|PROSITE-ProRule:PRU00159}.
CC -!- PTM: Ligand-binding increases phosphorylation on tyrosine residues.
CC Phosphorylation on tyrosine residues is mediated by
CC transphosphorylation by the catalytically active EPHB1 in a ligand-
CC independent manner. Tyrosine phosphorylation of the receptor may act as
CC a switch on the functional transition from cell adhesion/attraction to
CC de-adhesion/repulsion (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. Ephrin receptor subfamily. {ECO:0000255|PROSITE-
CC ProRule:PRU00159}.
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DR EMBL; L77867; AAB51430.1; -; mRNA.
DR EMBL; AK087423; BAC39868.1; -; mRNA.
DR EMBL; AK163823; BAE37507.1; -; mRNA.
DR EMBL; BC031924; AAH31924.1; -; mRNA.
DR CCDS; CCDS20051.1; -. [O08644-1]
DR RefSeq; NP_001139823.1; NM_001146351.1. [O08644-1]
DR RefSeq; NP_031706.3; NM_007680.4. [O08644-1]
DR AlphaFoldDB; O08644; -.
DR SMR; O08644; -.
DR BioGRID; 199479; 1.
DR STRING; 10090.ENSMUSP00000110380; -.
DR BindingDB; O08644; -.
DR ChEMBL; CHEMBL4739668; -.
DR GuidetoPHARMACOLOGY; 1834; -.
DR GlyGen; O08644; 1 site.
DR iPTMnet; O08644; -.
DR PhosphoSitePlus; O08644; -.
DR MaxQB; O08644; -.
DR PaxDb; O08644; -.
DR PeptideAtlas; O08644; -.
DR PRIDE; O08644; -.
DR ProteomicsDB; 275628; -. [O08644-1]
DR ProteomicsDB; 275629; -. [O08644-2]
DR ProteomicsDB; 275630; -. [O08644-3]
DR Antibodypedia; 32576; 542 antibodies from 31 providers.
DR DNASU; 13848; -.
DR Ensembl; ENSMUST00000114732; ENSMUSP00000110380; ENSMUSG00000029869. [O08644-1]
DR GeneID; 13848; -.
DR KEGG; mmu:13848; -.
DR UCSC; uc009bqa.2; mouse. [O08644-1]
DR CTD; 2051; -.
DR MGI; MGI:1096338; Ephb6.
DR VEuPathDB; HostDB:ENSMUSG00000029869; -.
DR eggNOG; KOG0196; Eukaryota.
DR GeneTree; ENSGT00940000160399; -.
DR HOGENOM; CLU_000288_141_4_1; -.
DR InParanoid; O08644; -.
DR OMA; PQGPSCM; -.
DR OrthoDB; 933071at2759; -.
DR PhylomeDB; O08644; -.
DR TreeFam; TF314013; -.
DR Reactome; R-MMU-2682334; EPH-Ephrin signaling.
DR Reactome; R-MMU-3928662; EPHB-mediated forward signaling.
DR Reactome; R-MMU-3928664; Ephrin signaling.
DR Reactome; R-MMU-3928665; EPH-ephrin mediated repulsion of cells.
DR BioGRID-ORCS; 13848; 0 hits in 75 CRISPR screens.
DR ChiTaRS; Ephb6; mouse.
DR PRO; PR:O08644; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; O08644; protein.
DR Bgee; ENSMUSG00000029869; Expressed in lip and 151 other tissues.
DR ExpressionAtlas; O08644; baseline and differential.
DR Genevisible; O08644; MM.
DR GO; GO:0009986; C:cell surface; IDA:MGI.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0043235; C:receptor complex; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:0005005; F:transmembrane-ephrin receptor activity; IBA:GO_Central.
DR GO; GO:0050798; P:activated T cell proliferation; IMP:MGI.
DR GO; GO:0007411; P:axon guidance; IBA:GO_Central.
DR GO; GO:0021952; P:central nervous system projection neuron axonogenesis; IBA:GO_Central.
DR GO; GO:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
DR GO; GO:0032092; P:positive regulation of protein binding; IMP:MGI.
DR GO; GO:2000525; P:positive regulation of T cell costimulation; IGI:MGI.
DR GO; GO:0002456; P:T cell mediated immunity; IMP:MGI.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR GO; GO:0001806; P:type IV hypersensitivity; IMP:MGI.
DR CDD; cd00063; FN3; 2.
DR Gene3D; 1.10.150.50; -; 1.
DR Gene3D; 2.60.40.10; -; 2.
DR InterPro; IPR027936; Eph_TM.
DR InterPro; IPR001090; Ephrin_rcpt_lig-bd_dom.
DR InterPro; IPR003961; FN3_dom.
DR InterPro; IPR036116; FN3_sf.
DR InterPro; IPR008979; Galactose-bd-like_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR001660; SAM.
DR InterPro; IPR013761; SAM/pointed_sf.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR011641; Tyr-kin_ephrin_A/B_rcpt-like.
DR InterPro; IPR016257; Tyr_kinase_ephrin_rcpt.
DR InterPro; IPR001426; Tyr_kinase_rcpt_V_CS.
DR Pfam; PF14575; EphA2_TM; 1.
DR Pfam; PF01404; Ephrin_lbd; 1.
DR Pfam; PF07699; Ephrin_rec_like; 1.
DR Pfam; PF00041; fn3; 2.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR Pfam; PF07647; SAM_2; 1.
DR PIRSF; PIRSF000666; TyrPK_ephrin_receptor; 1.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00615; EPH_lbd; 1.
DR SMART; SM00060; FN3; 2.
DR SMART; SM00454; SAM; 1.
DR SUPFAM; SSF47769; SSF47769; 1.
DR SUPFAM; SSF49265; SSF49265; 1.
DR SUPFAM; SSF49785; SSF49785; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS51550; EPH_LBD; 1.
DR PROSITE; PS50853; FN3; 2.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00790; RECEPTOR_TYR_KIN_V_1; 1.
DR PROSITE; PS00791; RECEPTOR_TYR_KIN_V_2; 1.
DR PROSITE; PS50105; SAM_DOMAIN; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; ATP-binding; Cell membrane; Glycoprotein; Membrane;
KW Nucleotide-binding; Receptor; Reference proteome; Repeat; Secreted; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..32
FT /evidence="ECO:0000250"
FT CHAIN 33..1014
FT /note="Ephrin type-B receptor 6"
FT /id="PRO_0000016838"
FT TOPO_DOM 33..591
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 592..612
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 613..1014
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 34..232
FT /note="Eph LBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00883"
FT DOMAIN 364..479
FT /note="Fibronectin type-III 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 480..575
FT /note="Fibronectin type-III 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316"
FT DOMAIN 663..912
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 941..1005
FT /note="SAM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00184"
FT MOTIF 1012..1014
FT /note="PDZ-binding"
FT /evidence="ECO:0000255"
FT BINDING 669..677
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT CARBOHYD 473
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 328
FT /note="P -> PCPALPLFTEHSRPEVC (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:8761299"
FT /id="VSP_003020"
FT VAR_SEQ 329..1014
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:8761299"
FT /id="VSP_003021"
FT VAR_SEQ 583
FT /note="P -> S (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:8761299"
FT /id="VSP_003022"
FT VAR_SEQ 584..1014
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:8761299"
FT /id="VSP_003023"
FT CONFLICT 527
FT /note="H -> Y (in Ref. 2; BAC39868)"
FT /evidence="ECO:0000305"
FT CONFLICT 544
FT /note="S -> T (in Ref. 3; AAH31924)"
FT /evidence="ECO:0000305"
FT CONFLICT 732
FT /note="T -> A (in Ref. 1; AAB51430)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1014 AA; 110107 MW; 1091796E1F68A842 CRC64;
MATEGTTGSG SRVVAGMVCS LWLLVLGSSV LALEEVLLDT TGETSEIGWL TYPPGGWDEV
SVLDDQRRLT RTFEACHVAG LPPGSGQDNW LQTHFVERRG AQRAHIRLHF SVRACSSLGV
SGGTCRETFT LYYRQADEPD GPDSIAAWHL KRWTKVDTIA ADESFPASSS SSSWAVGPHR
TGQRVGLQLN VKERSFGPLT QRGFYVAFQD TGACLALVAV KLFSYTCPSV LRAFASFPET
QASGAGGASL VAAVGTCVAH AEPEEDGVGG QAGGSPPRLH CNGEGRWMVA VGGCRCQPGH
QPARGDKLCQ ACPEGSYKAL AGNVPCSPCP ARSHSPDPAA PVCPCLQGFY RASSDPPEAP
CTGPPSAPRE LWFEVQGSAL MLHWRLPQEL GGRGDLLFNV VCKECGGHGE PSSGGMCRRC
RDEVHFDPRQ RGLTESRVLV GGLRAHVPYI LEVQAVNGVS ELSPDPPQAA AINVSTSHEV
PSAVPVMHQV SRAANSITVS WPQPEQTNGN ILDYQLRYYD QAEDESHSFT MTSETNTATV
TRLSPGHIYG FQVRARTAAG HGPYGGKVYF QTLPQGELSS QLPEKLSLVI GSILGALAFL
LLAAITVLAV IFQRKRRGTG YTEQLQQYSS PGLGVKYYID PSTYDDPCQA IRELAREVDP
TYIKIEEVIG AGSFGEVRRG RLQPRGRREQ AVAIQALWAG GAESLKMTFL GRAALLGQFQ
HPNILRLEGV VTKSRPVMVL TELMELGPLD SFLRQREGQF SSLQLVAMQR GVAAAMQYLS
SFAFVHRALS ARSVLVNSHL VCKVARLGHS PQGSSSLLRW AAPEVITHGK YTTSSDVWSF
GILMWEVMSY GERPYWDMNE QEVLNAIEQE FRLPPPPGCP PGLHLLMLDT WQKDRARRPH
FDQLVAAFDK MIRKPDTLQA EGGSGDRPSQ ALLNPVALDF PCLDSPQAWL SAIGLECYQD
NFSKFGLSTF SDVAQLSLED LPGLGITLAG HQKKLLHNIQ LLQQHLRQPG SVEV
